Variant chr3-44885368-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000296125.9(TGM4):c.63C>T(p.Ala21Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00328 in 1,613,756 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.017 ( 78 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 84 hom. )

Consequence

TGM4
ENST00000296125.9 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.65

Variant links:

Genes affected

TGM4 (HGNC:11780): (transglutaminase 4) Predicted to enable protein-glutamine gamma-glutamyltransferase activity. Predicted to be involved in peptide cross-linking. Predicted to act upstream of or within mating plug formation. Located in Golgi apparatus and collagen-containing extracellular matrix. [provided by Alliance of Genome Resources, Apr 2022]

TGM4 links:

TGM4 (HGNC:):

TGM4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 3-44885368-C-T is Benign according to our data. Variant chr3-44885368-C-T is described in ClinVar as [Benign]. Clinvar id is 775864.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.65 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TGM4	NM_003241.4 linkuse as main transcript	c.63C>T	p.Ala21Ala	synonymous_variant	2/14	ENST00000296125.9	NP_003232.2	P49221
TGM4	XM_011534042.3 linkuse as main transcript	c.198C>T	p.Ala66Ala	synonymous_variant	3/15		XP_011532344.1	A0A994J576

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TGM4	ENST00000296125.9 linkuse as main transcript	c.63C>T	p.Ala21Ala	synonymous_variant	2/14	1	NM_003241.4	ENSP00000296125.4	P49221
TGM4	ENST00000422219.5 linkuse as main transcript	n.63C>T		non_coding_transcript_exon_variant	2/6	1		ENSP00000403711.1	F8WCU8
TGM4	ENST00000705784.1 linkuse as main transcript	c.198C>T	p.Ala66Ala	synonymous_variant	3/15			ENSP00000516167.1	A0A994J576
TGM4	ENST00000490928.1 linkuse as main transcript	n.134C>T		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

AF:

0.0167

AC:

2549

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0584

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00576

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000220

Gnomad OTH

AF:

0.0110

GnomAD3 exomes

AF:

0.00443

AC:

1112

AN:

251064

Hom.:

AF XY:

0.00298

AC XY:

405

AN XY:

135698

show subpopulations

Gnomad AFR exome

AF:

0.0610

Gnomad AMR exome

AF:

0.00243

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.00278

GnomAD4 exome

AF:

0.00188

AC:

2746

AN:

1461454

Hom.:

Cov.:

AF XY:

0.00159

AC XY:

1159

AN XY:

726980

show subpopulations

Gnomad4 AFR exome

AF:

0.0644

Gnomad4 AMR exome

AF:

0.00307

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000336

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.0000953

Gnomad4 OTH exome

AF:

0.00477

GnomAD4 genome

AF:

0.0168

AC:

2552

AN:

152302

Hom.:

Cov.:

AF XY:

0.0159

AC XY:

1187

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0583

Gnomad4 AMR

AF:

0.00575

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000220

Gnomad4 OTH

AF:

0.0109

Alfa

AF:

0.00782

Hom.:

Bravo

AF:

0.0195

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 20, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.6

DANN

Benign

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over